Type I or insulin-dependent diabetes mellitus is the result of the destruction of the patients' insulin secreting cells, the .beta. cells of the pancreatic islets or islets of Langerhans. This destruction is mediated by an immunological process. Current treatment of type I diabetes consists in multiple daily injections of insulin to correct hyperglycemic episodes. This treatment however does not allows a sufficiently tight regulation of blood glucose levels and this lack of moment to moment control of glycemia leads over time to complications such as kidney failure, neuropathy, cardiac diseases and blindness.
Attempts to better control blood glucose could be achieved by transplantation of insulin secreting .beta. cells. Treatment of type I diabetic patients by transplantation of human pancreatic islets has been shown to be possible. However, treatment of a large number of diabetic patients with human islets is impractical due to the limited availability of pancreas from cadaver donors. Pig islets have been proposed as an alternative source for transplantation, but there is currently no way of reliably preparing sufficient pig islets to treat the millions of diabetic patients.
It has been proposed to use insulin secreting cell lines to overcome these problems. Indeed, the availability of insulin secreting cell lines with a proper control of insulin secretion would appear to present a number of advantages, namely the easy expansion of a cell stock and the precise control of the cells quality. Further, in theory, such cell lines could be generated from previously non insulin-secreting cell lines by genetic engineering. However, so far, the cell lines obtained by this approach secrete insulin constitutively or in a manner inappropriately controlled by variations in glucose concentrations (1).